Speaker

Jonathan Staley

University of Chicago

Molecular Genetics & Cell Biology

773-834-5886

jstaley@uchicago.edu

Proofreading for Errors in Pre-mRNA Splicing

The faithful expression of genes requires that cellular machinery select substrates with high specificity at each step in gene expression. Given the dominance of introns in eukaryotic genes, establishing fidelity is particularly important at the stage of nuclear pre-mRNA splicing, during which the spliceosome selects splice sites and excises intervening introns. Without specificity, the usage of alternative sites would yield insertions, deletions and frame shifts in messenger RNA. Our recent genetic and biochemical studies have significantly advanced our understanding of splicing fidelity. In particular, we have learned that ATP-dependent RNA unwindases play a general role in rejecting and discarding suboptimal substrates and that these factors serve as a paradigm for proofreading NTPases in other systems.